Adhesion of Leukocytes to Growing Arterial Thrombi

1998 ◽  
Vol 80 (11) ◽  
pp. 852-858 ◽  
Author(s):  
Helge Einar Roald ◽  
Torstein Lyberg ◽  
Inger Anne Hagberg
Keyword(s):  
Ex Vivo ◽  
Leukocyte Adhesion ◽  
Active Role ◽  
Short Term ◽  
Ex Vivo Model ◽  
Hla Dr ◽  
Rate Characteristic ◽  
Platelet Thrombi ◽  
Contrast Flow

SummarySince the role of leukocytes found present in thrombi and haemo-static plugs is not clearly understood, we have investigated the interaction between leukocytes and growing thrombi in a human ex vivo model of arterial thrombogenesis. At a wall shear rate characteristic of moderately stenosed arteries (2600 s–1), granulocytes selectively accumulated at the luminal surface of platelet thrombi. The leukocyte adhesion seemed independent of fibrin formation and was clearly correlated to thrombus growth and platelet activation. In contrast, flow cytometry revealed that the expression of adhesion molecules (CD11a, CD11b, CD11c, CD3, CD14, CD62L, HLA-DR and binding of fibrinogen) on the surface of circulating leukocytes passing the thrombi was, on short term conditions (15 min), independent of thrombus growth. The adhered granulocytes probably play a pivotal role in limiting the size of the evolving thrombi, as suggested by our electron micrographs of the arterial thrombi showing lysed and phagocytosed platelets. Thus, granulocytes might play an active role in the acute/semiacute phase of local thromboregulation.

scholarly journals Effect of Fluoxetine and Paroxetine on Intestinal Motility in Presence of Ondansetron in ex-vivo Model

2020 ◽  
Vol 1 (3) ◽  
pp. 5
Author(s):  
Ayesha Afzal ◽  
Ammara Khan ◽  
Khalida Ajmal ◽  
Abeera Sikandar ◽  
Saima Rafiqu ◽  
...  
Keyword(s):  
Intestinal Motility ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Contractile Response ◽  
Ex Vivo ◽  
Ex Vivo Model ◽  
Rabbit Ileum ◽  
Medical College ◽  
Fixed Concentration ◽  
Antidepressant Effects

Objective: To understand the effects of fluoxetine and paroxetine with ondansetron on the intestinal motility of rabbit ileum. Study Design: Observational study. Place and Duration of Study: The study was conducted from March to April 2018 in a multidisciplinary lab of Army Medical College, Rawalpindi.Materials and Methods: The contractile effect of intestinal motility was recorded in the power lab. Subjects were twenty four healthy rabbits (Oryctolagus Cuniculus). Semi log dose-response curve was constructed for increasing concentrations of serotonin, ondansetron, fluoxetine, and paroxetine (10-9 to 10-6 M) alone and then in the presence of a fixed concentration of ondansetron (10-6 M) to observe the modulatory role of ondansetron. The serotonin mediated contractions were taken as control.Results: Ondansetron and serotonin caused an increase in the contractile response of rabbits ileum. A depressive response was observed when the contractions were recorded with increased concentration of fluoxetine and paroxetine in the presence of ondansetron. Conclusion: Ondansetron when used concomitantly with selective serotonin reuptake inhibitors(SSRIs), abolishes their antidepressant effects by causing a decrease in the intestinal motility of rabbit ileum.

scholarly journals Unravelling the role of Mesenchymal Stem/Stromal Cells Secretome in intervertebral disc degeneration in a pro-inflammatory/degenerative ex vivo model

2020 ◽  
Author(s):  
JR Ferreira ◽  
GQ Teixeira ◽  
E Neto ◽  
C Ribeiro-Machado ◽  
AM Silva ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Stromal Cells ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Ex Vivo Model

Abstract The authors have withdrawn this preprint due to author disagreement.

scholarly journals Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+ Cells in Human Rectal Mucosa

2005 ◽  
Vol 79 (9) ◽  
pp. 5762-5773 ◽  
Author(s):  
Kevin B. Gurney ◽  
Julie Elliott ◽  
Hoorig Nassanian ◽  
Carol Song ◽  
Elizabeth Soilleux ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Rectal Mucosa ◽  
Virus Binding ◽  
Mucosal Transmission ◽  
Hla Dr ◽  
Immunodeficiency Virus

ABSTRACT The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+ cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ cells can bind and transfer more virus than the HLA-DR+/DC-SIGN− cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+ cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r = 0.58, P < 0.002; n = 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3β. Thus, an increased IL-10 environment could render DC-SIGN+ cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.

Tu1919 A NOVEL INTEGRATED IN VIVO/ EX VIVO MODEL TO STUDY THE EFFECT OF SHORT-TERM COLONIC BUTYRATE EXPOSURE ON HUMAN COLONIC PERMEABILITY

2020 ◽  
Vol 158 (6) ◽  
pp. S-1219
Author(s):  
Mathias W. Tabat ◽  
Tatiana M. Marques ◽  
John-Peter Ganda Mall ◽  
Richard A. Forsgård ◽  
Robert J. Brummer ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Short Term ◽  
Ex Vivo Model

Phospholipase C signaling tonically represses basal atrial natriuretic factor secretion from the atria of the heart

2013 ◽  
Vol 304 (10) ◽  
pp. H1328-H1336 ◽  
Author(s):  
Astra I. Chang ◽  
Monica Forero McGrath ◽  
Adolfo J. de Bold
Keyword(s):  
Phospholipase C ◽  
Atrial Natriuretic Factor ◽  
Ex Vivo ◽  
Electrolyte Balance ◽  
Protein Signaling ◽  
Basal Secretion ◽  
Ex Vivo Model ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

The cardiac hormone atrial natriuretic factor (ANF or ANP) plays significant, well-established roles in a large number of physiological and pathophysiological processes, including water and electrolyte balance, blood pressure regulation, and cardiovascular growth. Understanding the regulation of its production and secretion by atrial cardiomyocytes is incomplete. We have previously established a significant role of Gi/o protein signaling in modulating ANF secretion as promoted by stretch of the atrial myocardium. In the present study, we investigated the role of Gq protein signaling and its relationship to Gi/o protein signaling using pharmacological manipulation of proximal effectors of Gαq in an ex vivo model of spontaneously beating rat atria. Phospholipase C (PLC) and protein kinase C (PKC) inhibitors dramatically increased basal secretion of ANF. Furthermore, although atrial wall stretch is a potent stimulus for secretion, stretch unexpectedly reduced ANF secretion to basal levels under PLC and PKC inhibitory conditions. Inhibition of the inositol triphosphate receptor did not appear to affect basal secretion but dose-dependently blocked stretch-secretion coupling. The results obtained demonstrate that the PLC and PKC signaling cascades play important albeit unexpected roles in the regulation of basal and stimulated ANF secretion and suggest interplay between the Gq and Gi/o protein signaling pathways.

scholarly journals Downregulation of Mitochondrial TSPO Inhibits Mitophagy and Reduces Enucleation During Human Terminal Erythropoiesis

2020 ◽  
Vol 21 (23) ◽  
pp. 9066
Author(s):  
Martina Moras ◽  
Claude Hattab ◽  
Pedro Gonzalez-Menendez ◽  
Suella Martino ◽  
Jerome Larghero ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Active Role ◽  
Translocator Protein ◽  
Macromolecular Complex ◽  
Anion Channels ◽  
Voltage Dependent ◽  
Erythroid Maturation ◽  
Immortalized Cell ◽  
Pleiotropic Functions

Translocator protein (TSPO) and voltage dependent anion channels (VDAC) are two proteins forming a macromolecular complex in the outer mitochondrial membrane that is involved in pleiotropic functions. Specifically, these proteins were described to regulate the clearance of damaged mitochondria by selective mitophagy in non-erythroid immortalized cell lines. Although it is well established that erythroblast maturation in mammals depends on organelle clearance, less is known about mechanisms regulating this clearance throughout terminal erythropoiesis. Here, we studied the effect of TSPO1 downregulation and the action of Ro5-4864, a drug ligand known to bind to the TSPO/VDAC complex interface, in ex vivo human terminal erythropoiesis. We found that both treatments delay mitochondrial clearance, a process associated with reduced levels of the PINK1 protein, which is a key protein triggering canonical mitophagy. We also observed that TSPO1 downregulation blocks erythroblast maturation at the orthochromatic stage, decreases the enucleation rate, and increases cell death. Interestingly, TSPO1 downregulation does not modify reactive oxygen species (ROS) production nor intracellular adenosine triphosphate (ATP) levels. Ro5-4864 treatment recapitulates these phenotypes, strongly suggesting an active role of the TSPO/VDAC complex in selective mitophagy throughout human erythropoiesis. The present study links the function of the TSPO/VDAC complex to the PINK1/Parkin-dependent mitophagy induction during terminal erythropoiesis, leading to the proper completion of erythroid maturation.

An Ex Vivo Investigation into the Release of Fluoride from Fluoride-containing Orthodontic Bonding Composites

1994 ◽  
Vol 21 (3) ◽  
pp. 239-243 ◽  
Author(s):  
Sarah H. A. Ghani ◽  
Stephen L. Creanor ◽  
John K. Luffingham ◽  
Richard H. Foye
Keyword(s):  
Similar Pattern ◽  
Ex Vivo ◽  
Composite Resins ◽  
Fluoride Release ◽  
Short Term ◽  
Ex Vivo Model ◽  
The Third ◽  
Orthodontic Bonding

This study was concerned with an evaluation of fluoride release from commercially available orthodontic bonding composite resins, known as Reliance® and Mirage Dual Cure®, which are claimed to release ionic floride. Forty-eight premolar teeth had brackets bonded with four different composite resins—Mirage Dual Cure®, Reliance®, Right-on® and Heliosit®. They were then immersed in a demineralizing solution. The amount of fluoride released from the composites into the solution was measured. The results indicated that Mirage Dual Curereg; released statistically significant amounts of fluoride over the first 2 days. A similar pattern was noted with Reliance® albeit releasing a lesser amount. From the third day onwards, fluoride release levelled out to concentrations similar to those of the two control materials, Right-on® and Heliosit®(i.e. 0·09 ppm). Fluoride-releasing composite resins, therefore, failed to demonstrate any potential long-term fluoride release within the ex vivo model. Even in the short term, the amount of fluoride released was very small.

scholarly journals Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection

2001 ◽  
Vol 90 (6) ◽  
pp. 2257-2268 ◽  
Author(s):  
Brendan J. Collins ◽  
Matthew G. Blum ◽  
Richard E. Parker ◽  
Andrew C. Chang ◽  
Kelly S. A. Blair ◽  
...  
Keyword(s):  
Median Survival ◽  
Human Blood ◽  
Ex Vivo ◽  
Loss Of Function ◽  
Ex Vivo Model ◽  
Necrosis Factor ◽  
Abrupt Rise ◽  
Pulmonary Intravascular Macrophages ◽  
Initial Perfusion

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacute lung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH2O · ml−1· min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverine significantly blunted the rise in PVR (<0.2 cmH2O · ml−1· min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O · ml−1· min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages with dichloromethyl bisphosphonate in liposomes, but not Pall filtration of the human blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation (<0.3 cmH2O · ml−1· min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.

scholarly journals EFFECTS OF FEMALE BLOOD AUTOSERUM ON ALLOGENIC INTERACTIONS IN SHORT-TERM LYMPHOCYTE CULTURES OF PARENTS HAVING CHILDREN WITH CONOTRUNCAL HEART MALFORMATIONS

2019 ◽  
Vol 8 (3) ◽  
pp. 60-71
Author(s):  
S. V. Gorshkova ◽  
S. A. Shmulevich ◽  
A. V. Shabaldin ◽  
N. S. Deeva ◽  
A. V. Tsepokina ◽  
...  
Keyword(s):  
Immune Response ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Study Group ◽  
Short Term ◽  
Hla Dr ◽  
Lymphocyte Cultures ◽  
Heart Malformations ◽  
Humoral Regulation

Highlights The findings of this original study ensure the detection of violations in the humoral regulation of the maternal immune interactions with semiallogeneic fetus, considered as a risk factor for developing sporadic conotruncal heart malformations in the next generation.Aim To study the role of female autoserum blood in limiting allogeneic interactions in short-term lymphocyte cultures of parents having children with conotruncal heart malformations.Methods 21 married couples (the study group) with children suffering from conotrucnal heart malformations (Tetralogy of Fallot) without chromosomal diseases were examined. The control group consisted of 21 families with three or more healthy children. The immune response in a mixed lymphocyte culture of parents was assessed by the increase in HLA-DR expression in the mixed culture with respect to spontaneous lymphocyte cultures. Primary staining of female and male lymphocytes with monoclonal antibodies to CD45, conjugated with various fluorescent dyes (PC-5 and PC-7), allowed assessing the immune response of female lymphocytes to male and vice versa.Results The effects of female autoserum on the mixed lymphocyte culture of parents were assessed. The obtained results reported that the birth of children with conotruncal heart malformations is associated with the interfering effect of female autoserum on HLA-DR expression on subpopulations of female lymphocytes (CD3+, HLA-DR+) and the activating effect on subpopulations of female lymphocytes (CD3-, HLA-DR+). The observed role of female autoserum in the study group may be associated with the absence of HLA-DR-blocking autoantibodies and high synthesis of cytokines by T2 and T3 helper lymphocytes.Conclusion The effects of female autoserum on allogeneic lymphocyte interactions of parents may be observed in short-term mixed lymphocyte cultures. The evaluation of the activating and interfering effects ensures timely identification of any violations in the humoral regulation of the maternal immune interactions with the HLA semiallogenic fetus, considered as a risk factor for developing sporadic conotruncal heart malformations in the next generation.

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